PDF(Pubmed)
Abstract：
Cellular senescence, a state of irreversible growth arrest, is implicated in various age-related pathologies, including skin aging. In this study, we investigated the role of CLCA2, a calcium-activated chloride channel accessory protein, in cellular senescence and its implications for skin aging. Utilizing UVB and Nutlin3a-induced senescence models, we observed the upregulation of CLCA2 at both transcriptomic and proteomic levels, suggesting its involvement in senescence pathways. Further analysis revealed that the depletion of CLCA2 led to accelerated senescence onset, characterized by classic senescence markers and a unique secretome profile. In 3D skin equivalent models, SEs constructed with CLCA2 knockdown fibroblasts exhibited features reminiscent of aged skin, underscoring the importance of CLCA2 in maintaining skin homeostasis. Our findings highlight CLCA2 as a novel regulator of cellular senescence and its potential implications for skin aging mechanisms.
摘要：
细胞衰老,不可逆转的生长停滞状态，与各种年龄相关的病理有关，包括皮肤老化。在这项研究中,我们研究了CLCA2的作用，CLCA2是一种钙激活的氯离子通道辅助蛋白，细胞衰老及其对皮肤老化的影响。利用UVB和Nutlin3a诱导的衰老模型，我们观察到CLCA2在转录组和蛋白质组水平的上调，表明它参与了衰老途径。进一步的分析表明，CLCA2的耗竭导致衰老加速，以经典的衰老标记和独特的分泌组特征为特征。在3D皮肤等效模型中，用CLCA2敲低成纤维细胞构建的SE表现出让人联想到老化皮肤的特征，强调CLCA2在维持皮肤稳态中的重要性。我们的发现强调了CLCA2作为细胞衰老的新型调节剂及其对皮肤衰老机制的潜在影响。
